3-氨基-6-[4-[[2-(二甲基氨基)-1-甲基乙基]磺酰基]苯基]-N-苯基-2-吡嗪羧酰胺 | 1286238-55-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 3-氨基-6-[4-[[2-(二甲基氨基)-1-甲基乙基]磺酰基]苯基]-N-苯基-2-吡嗪羧酰胺
• 英文名称: 3-amino-6-(4-((1-(dimethylamino)propan-2-yl)sulfonyl)phenyl)-N-phenylpyrazine-2-carboxamide
• 英文别名: 3-Amino-6-[4-[[2-(dimethylamino)-1-methylethyl]sulfonyl]phenyl]-N-phenyl-2-pyrazinecarboxamide；3-amino-6-[4-[1-(dimethylamino)propan-2-ylsulfonyl]phenyl]-N-phenylpyrazine-2-carboxamide
• CAS: 1286238-55-8
• 化学式: C₂₂H₂₅N₅O₃S
• 分子量: 439.538
• InChiKey: GNEFGLFGNKFHAR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  127
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4-溴苯基 2-氯乙基砜 在 四(三苯基膦)钯 、 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 potassium acetate 、 sodium carbonate 、 potassium carbonate 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 21.25h， 生成 3-氨基-6-[4-[[2-(二甲基氨基)-1-甲基乙基]磺酰基]苯基]-N-苯基-2-吡嗪羧酰胺
  参考文献：
  名称：

  Discovery of Potent and Selective Inhibitors of Ataxia Telangiectasia Mutated and Rad3 Related (ATR) Protein Kinase as Potential Anticancer Agents

  摘要：

  DNA-damaging agents are among the most frequently used anticancer drugs. However, they provide only modest benefit in most cancers. This may be attributed to a genome maintenance network, the DNA damage response (DDR), that recognizes and repairs damaged DNA. ATR is a major regulator of the DDR and an attractive anticancer target. Herein, we describe the discovery of a series of aminopyrazines with potent and selective ATR inhibition. Compound 45 inhibits ATR with a K-i of 6 nM, shows >600-fold selectivity over related kinases ATM or DNA-PK, and blocks ATR signaling in cells with an IC50 of 0.42 mu M. Using this compound, we show that ATR inhibition markedly enhances death induced by DNA-damaging agents in certain cancers but not normal cells. This differential response between cancer and normal cells highlights the great potential for ATR inhibition as a novel mechanism to dramatically increase the efficacy of many established drugs and ionizing radiation.

  DOI：

  10.1021/jm101488z

文献信息

• [EN] INHIBITING ATAXIA TELANGIECTASIA AND RAD3-RELATED PROTEIN (ATR)<br/>[FR] INHIBITION DE LA PROTÉINE ASSOCIÉE À L'ATAXIE TÉLANGIECTASIE ET À RAD3 (ATR)
  申请人：MERRIMACK PHARMACEUTICALS INC

  公开号：WO2017123588A1

  公开（公告）日：2017-07-20

  Novel compounds inhibiting ATR protein kinase include compounds of formula (I) disclosed herein, as well as liposome formulations comprising ATR protein kinase inhibitor compounds. The compositions are useful for the treatment of cancer.

  新型化合物抑制ATR蛋白激酶，包括公式（I）所披露的化合物，以及包含ATR蛋白激酶抑制剂化合物的脂质体配方。该组合物对治疗癌症有用。
• Inhibiting ataxia telangiectasia and Rad3-related protein (ATR)
  申请人：Merrimack Pharmaceuticals, Inc.

  公开号：US10570119B2

  公开（公告）日：2020-02-25

  Novel compounds inhibiting ATR protein kinase include compounds of formula (I) disclosed herein, as well as liposome formulations comprising ATR protein kinase inhibitor compounds. The compositions are useful for the treatment of cancer.

  抑制 ATR 蛋白激酶的新型化合物包括本文公开的式 (I) 化合物以及包含 ATR 蛋白激酶抑制剂化合物的脂质体制剂。这些组合物可用于治疗癌症。
• INHIBITING ATAXIA TELANGIECTASIA AND RAD3-RELATED PROTEIN (ATR)
  申请人：Merrimack Pharmaceuticals, Inc.

  公开号：EP3402532A1

  公开（公告）日：2018-11-21